Clinical research on the pathologies of sleep and basic research on the pathologies of sleep form the heart of the proposed research program. The major prongs of the program are as follows: Research on Normal and Pathological Sleepiness/Alertness. A theoretical optimal adjustment to the 24-hour environment is to be very alert and energetic in the daytime and very sleepy, or soundly asleep, at night. The most predictable and pervasive interaction of sleep and wakefulness is through the induction of sleepiness in response to various schedules of sleep loss. At the present time, a very broad program has evolved with in-depth studies of the basic nature of the sleepiness/alertness dimension and its major determinants; amount an quality of sleep at night, circadian phase, age, drugs, and various pathologies. We will also investigate the role of this dimension in human performance. Narcolepsy Research. Prior efforts have led to the development of a pure, reliably reproducing strain of Doberman pinscher narcolepsy. The availability of an unlimited supply of animals constitutes a breakthrough and opens up the problem of narcolepsy to a variety of decisive investigations. We will carry out a series of biochemical studies capitalizing on prior research which documents specific CNS abnormalities in canine narcolepsy. Sleep-Related Respiratory Disturbance and Aging. We are investigating the relationship of sleep apnea and hypopnea to a variety of other functions in elderly populations. We emphasize longitudinal studies and cognitive studies. Other areas are cardiovascular factors and daytime sleepiness. We are also developing research programs in chronobiology, cellular neurophysiology, sleep and wakefulness in the teaching nursing home and a suitable animal model for research on sleep in the aged organism.